Ohio University Heritage College of Osteopathic Medicine Office of Research & Grants Research & Scholarly Advancement Fellowship Summer, 2014 APPLICATION DEADLINE: February 10, 2014 ACCEPTANCE NOTIFICATION: March 7, 2014 PROGRAM DATES: June 2 - August 8, 2014 Since 1978, OU-HCOM has sponsored a program to provide summer research experiences to medical students. We invite you to help us celebrate the past 36 years and continue the tradition in the future. Summary of Program The core of the program is a research project that you will pursue under faculty direction. Projects can include contributing to ongoing faculty research in the laboratory or clinic or initiation of your own project under faculty direction. In addition to your research project, you will be required to attend the program orientation, seminars on various research topics, and the program closing session; submit project progress reports; and prepare and present a poster on the project at the OU-HCOM Research Day during the fall semester following the fellowship program. The fellowship pays $3,000 to assist fellows with living expenses over the ten-week program. Fellowship payments will be paid intermittently throughout the program and will be paid through the Disbursement Office, located in Chubb Hall. Upon successful completion of the fellowship program, fellows will receive one hour of academic credit. There will be no tuition cost to the fellows for participation in the program and the program will be graded on a pass/fail basis. Upon acceptance into the program, fellows will be required to register for the fellowship with the permission of the Office of Research & Grants. Funding for up to four RSAF fellowship awards will be provided by the Osteopathic Heritage Foundations. Funding for up to eleven RSAF fellowship awards will be provided by OU-HCOM. Additional RSAF fellowship awards may be made based on the availability of funds. Eligibility All students who will successfully complete the Year 1 medical school curriculum by the end of spring semester 2014 are invited to apply for the Research & Scholarly Advancement Fellowship (RSAF) program. Students must also be in good professional and judicial standing at the time of application through the completion of the program (OU-HCOM Research Day). This ten-week summer program is designed to introduce osteopathic students to basic science and clinical research and scholarly activities under the guidance of an OU-HCOM faculty mentor. Student Selection Faculty mentors will be provided with the applications for students who have applied to work with the mentor and on his/her research project. After review of applications and consultation with applicants, mentors are required to rank applicants in order of preference. After all mentor rankings have been received, the Office of Research & Grants will then review rankings and place students. We will make our best effort to place students according to the faculty mentor’s preference, but there is no guarantee. Final placement of students will be made at the discretion of the Office of Research & Grants. Exceptions to the student selection process will be made for students participating in the DO/PhD program through the OU-HCOM Office of Advanced Studies. These students are not exempt from the application process, but will be guaranteed placement within the RSAF program due to their required participation as part of the DO/PhD program. Conditions of Appointment Appointment of a fellow is contingent upon successful completion of the Year 1 medical school curriculum by the end of spring semester 2014 and that the student is in good professional and judicial standing at the time of application through the completion of the program (OU-HCOM Research Day). Fellows are expected to conduct research according to the highest scientific and ethical standards and in compliance with all applicable laws, regulations, and policies regarding protection of human research subjects, humane care and use of laboratory animals, and laboratory safety. Application Process 1. 2. 3. Read the faculty mentor/research project profiles provided. You must select only from faculty mentors/research projects included in this application package. Contact the faculty mentor(s) with whom you may be interested in working and talk with them about your interests. Students must consult with potential faculty mentors, in person, prior to submission of the student application package. Complete the Project Discussion Form (signed by both you and your proposed faculty mentor) and return it as part of your application package. One form must be completed for each faculty mentor/research project for which you are applying. Complete and return the RSAF application package (provided), no later than Monday, February 10, 2014. Application package includes: Document Checklist Form – Applicant must sign this form and insure that all documents are included Program Application Form – Applicant must sign this form Driver’s License and Ohio University Identification Card – Copy of driver’s license and OU ID card Résumé/Curriculum Vitae – Must include: academic history, employment history, research experience, list of honors/awards received, and publications Project Discussion Form(s) – Applicant and Faculty Mentor(s) must sign this form. One form is required for each project for which the student applies. Submission Procedures Application Deadline: February 10, 2014 All forms must be submitted in one large envelope by the application deadline. Electronic applications will not be accepted. Please deliver application envelopes to: Jessica Wingett Office of Research & Grants 234 Grosvenor Hall IMPORTANT DATES Application Deadline Acceptance Notification Program Begins/Orientation Session Research Seminars Program Ends/Closing Session February 10, 2014 March 7, 2014 (approximate) June 2, 2014 June 2-6, 2014 August 8, 2014 For more information, contact: Jessica Wingett, Program Director, at 740-593-2336 or [email protected] Ohio University Heritage College of Osteopathic Medicine Office of Research & Grants Research & Scholarly Advancement Fellowship Summer, 2014 CHECKLIST To the Applicant: Please complete and sign below. Make sure to have ALL requirements in one sealed envelope. Incomplete application packages will NOT be reviewed. Document Checklist Form – Sign below and include this form in application envelope Program Application Form Driver’s License and Ohio University Identification Card – Copy of driver’s license and OU ID card Résumé/Curriculum Vitae – Must include: academic history, employment history, research experience, list of honors/awards received, and publications Project Discussion Form – Applicant and Faculty Mentor(s) must sign this form. One form is required for each project for which the student applies. I verify that I have included all of the above documents in my application package. I understand that if all of the above documents are not included, my application will not be reviewed. Name of Applicant: __________________________________________________________________________________________ ______________________________________________ Signature of Applicant ___________________________________________ Date Ohio University Heritage College of Osteopathic Medicine Office of Research & Grants Research & Scholarly Advancement Fellowship Summer, 2014 PROGRAM APPLICATION General Information Applicant’s Name (Last, First, Middle Initial) Daytime Phone Date of Birth (mm/dd/yy) Evening/Alternate Phone OU PID # Email (OHIO) Current Mailing Address (Street and Apt. or PO Box Number, City, State, Zip Code) Permanent Mailing Address (if different than above) Program Preferences Choose faculty mentor/research project in preference order (maximum 2 options) 1. 2. Colleges or Universities Attended: (start with most recent) Name of School, City, State Degree Date of Degree Major Minor 1. Describe honors, hobbies, special interests or previous work experience that you would like considered. (use additional pages as needed) 2. Have you done research or independent study previously? If yes, please describe: 3. Publications? (List) YES NO 4. Why did you decide to apply for this program? How will it help you? Use additional pages as needed Certification & Eligibility Verification I certify that the above information is accurate and true to the best of my knowledge. I give permission to the Ohio University Heritage College of Osteopathic Medicine Office of Research & Grants to share this information for the purpose of recruitment, placement, monitoring, and evaluation. I certify that I meet all the eligibility criteria stated in the Research & Scholarly Advancement Fellowship Program Summary. Name of Applicant: ___________________________________________________________________________________________ _______________________________________________ Signature of Applicant ___________________________________________ Date Ohio University Heritage College of Osteopathic Medicine Office of Research & Grants Research & Scholarly Advancement Fellowship Summer, 2014 PROJECT DISCUSSION FORM This form is designed to insure that students and faculty members meet (in person) to discuss projects that interest students prior to application. This meeting will provide students and faculty members with an opportunity to meet outside of the classroom, discuss the project and the fellow’s role in the project, and allow for questions. This form must be completed by the student, signed by both the student and faculty mentor and included in the application package. One form must be completed and included for each project for which the student applies. Applicant Name Faculty Mentor Project Title Meeting Date 1. Overall Objective/Goal of the Project 2. Role of Fellow in Project 3. Role of Fellow in Lab/Clinic 4. Other (if applicable) _______________________________________________ Signature of Applicant _______________________________________________ Date _______________________________________________ Signature of Faculty Mentor _______________________________________________ Date Research & Scholarly Advancement Fellowship Summer, 2014 Faculty Mentor and Research Project Profile Jane Broecker, MD Department of Obstetrics & Gynecology River Rose Ob/Gyn 75 Hospital Drive, Suite 260, Athens (740) 818-6267 (Cell) Email: [email protected] Project Classification: Clinical Research & Social/Behavioral Research Techniques and/or skills that the student will learn: 1. Data Analysis 2. Writing a research paper 3. Working with computer specialists 4. Informed Consent 5. Potentially, study design and the IRB process Project Title: Internet Impressions of Long Acting Contraceptive Methods: College students' impressions of internet based health information concerning contraceptive devices. Project Description: My ongoing research is about long acting contraceptives and our ongoing project will involve data analysis of surveys administered by our student from last summer, Robin Fuchs. We will be working with Joan Jurich to code the responses and analyze the data collected. We will write a paper about our findings and how knowledge and attitudes toward contraceptives may affect decision making about birth control, and how parental influences affect patient attitudes. My new study will be a study about how female (and possibly male) college students interact with the internet to find information on short acting and long acting methods of contraception. This will involve working with computer specialists, learning how to contact and consent patients for the study, and analysis of the data collected. It has not yet been submitted for IRB approval, but I anticipate approval in the Spring. I would also welcome a student to create his or her own study and go through the design, creation and IRB approval of a simple study, if he or she desires. Research & Scholarly Advancement Fellowship Summer, 2014 Faculty Mentor and Research Project Profile Brian Clark, PhD Department of Biomedical Sciences 251 Irvine Hall (740) 593-2354 Email: [email protected] Project Classification: Basic Science & Clinical Research Techniques and/or skills that the student will learn: 1. Clinical trial management 2. EMG 3. Brain stimulation Project Description: Dr. Clark, and other scientists affiliated with the Ohio Musculoskeletal and Neurological Institute (OMNI), embrace a team-based approach to science. Accordingly, students rotating through OMNI will be asked to assist will all ongoing research projects as needed. Some of these will be massive ongoing projects and others will be projects that are just starting up and/or in development. At this time, it is not possible to state exactly which projects the student will be most heavily engaged as it will depend on the status of projects, grants, etc. The Ohio Musculoskeletal and Neurological Institute’s mission is to improve the diagnosis, treatment, and prevention of musculoskeletal and neurological disorders. Accordingly, OMNI scientists conduct basic and clinical research pertaining to the advancement of musculoskeletal and neurological health. OMNI has strong programmatic efforts in two research divisions: 1) musculoskeletal and neurological pain disorders, and 2) healthy aging. The research across these two divisions has an overarching aim of developing interventions that remove barriers to independent physical mobility and ultimately reduce disability. Potential studies for involvement range from: 1) clinical trials on the effectiveness and physiological effects of manual therapies to treat low back pain; 2) the safety and effectiveness of a new compound (myostatin-inhibitor) to treat muscle wasting disorders; 3) the mechanisms of perceived fatigue in aging; 4) utilization of advanced medical imaging techniques to quantify lumbar spine segmental motion; and 5) use of transcranial direct current stimulation to enhance muscle endurance capacity. Research & Scholarly Advancement Fellowship Summer, 2014 Faculty Mentor and Research Project Profile Leslie Consitt, PhD Department of Biomedical Sciences 228 Irvine Hall (740) 593-2404 Email: [email protected] Project Classification: Basic Science & Clinical Research Techniques and/or skills that the student will learn: 1. Clinical skills with humans – Subject screening for diabetes study, insulin sensitivity testing, blood pressure 2. Assist with skeletal muscle biopsies – Sample processing 3. Metabolic studies in human skeletal muscle (i.e. oxygen consumption in human skeletal muscle) (Diabetics vs Healthy Controls) 4. Western blot techniques for the examination of protein activity/content in human skeletal muscle tissue (Diabetics vs Healthy Controls) Project Title: The Role of Skeletal Muscle SMAD2/3 in Insulin Resistance Project Description: Insulin resistance is considered a significant public health concern and is believed to contribute to a number of co-morbidities including diabetes, cardiovascular disease, and hypertension. In the United States, insulin resistance has reached epidemic proportions causing considerable anxiety regarding the strain that will be placed on the health care system in the near future. Despite this concern, little is known regarding the cellular mechanisms that contribute to insulin resistance, particularly in the primary target tissue of insulin, skeletal muscle. The research conducted in my laboratory identifies and examines the mechanism(s) contributing to skeletal muscle insulin resistance. Research in animal models suggests that myostatin, a member of the transforming growth factor-β (TGF-β) superfamily, may promote insulin resistance through the phosphorylation of the conical myostatin signaling pathway mothers against decapentaplegic homolog (SMAD2/3). Unfortunately, no known research has been conducted in Type 2 diabetics to determine if myostatin intracellular signaling, specifically the SMAD2/3 pathway, is up-regulated and contributes to skeletal muscle insulin resistance. This fellowship will provide the individual with the opportunity to perform a number of research techniques. The primary objective of the fellowship will be to perform metabolic testing in the skeletal muscle of 1) lean healthy individuals; 2) obese individuals and 2) obese type 2 diabetics to determine a cellular mechanism contributing to insulin resistance. The primary focus of the fellowship will be to perform western blot analysis on the skeletal muscle of these individuals to determine an association between SMAD2/3 activity/protein and insulin resistance. Other metabolic techniques will include the measurement of mitochondrial oxygen consumption in skeletal muscle to determine a possible mechanism through which SMAD2/3 inhibits insulin sensitivity. The fellow will also have the opportunity to perform clinical skills when assisting with subject screening (i.e., interviewing, blood pressure, etc.). This fellowship will expose the individual to both clinical and basic science. Research & Scholarly Advancement Fellowship Summer, 2014 Faculty Mentor and Research Project Profile David Drozek, DO Department of Specialty Medicine Parks Hall (678) 447-2509 (Cell) Email: [email protected] Project Classification: Clinical Research Techniques and/or skills that the student will learn: 1. Chart review and data collection 2. Statistical analysis 3. Literature review 4. Scientific paper writing Project Title: Evaluation of effectiveness of a new hospital based lifestyle medicine clinic. Project Description: The RSAF fellow will review the results of three iterations of a new lifestyle medicine clinic funded as a community benefit program by Doctors Hospital Nelsonville / Ohio Health. The final iteration will be running during the winter/spring semester 2014, and the selected fellow will be encouraged to visit at least one session of the clinic to better understand the format. The study will compare biometrics (BMI, blood pressure, fasting glucose and lipids) as well as activity and depression scale surveys done before and near the end of participation in the clinic. The first two clinic populations were small. There have been several modifications to the program. The third iteration, which will begin in February 2014, will likely be larger and more mature in its programming, and will be the primary focus of the statistical evaluation. The clinic is a series of 12 weekly sessions consisting of video content, live lecture, discussion, food sampling, and exercise. The emphasis of the teaching is a healthy diet, exercise, stress reduction and elimination of unhealthy habits. The focus of the class is to introduce sustainable lifestyle changes that will prevent and/or reverse chronic Western diseases, such as overweight/obesity, hypertension, diabetes, coronary artery disease, elevated cholesterol, many cancers, and others. Each week consists of a specific theme to inform the participants of the scientific evidence, and to encourage them to make healthy changes. Each session ends with setting goals for the next week, and begins with reviewing the goals from the prior week. Five to ten minutes of exercise are included based on video segments available free on the Internet, to give participants knowledge of a spectrum of exercise aids available to them. A healthy food item is prepared in advance for the participants. They are given the recipe, and in many cases watch a video of the food preparation. Shopping skills, label reading, and practical information on many chronic disease entities are taught. The materials utilized in the class include many free resources from Physicians Committee for Responsible Medicine, Activity Bursts Everywhere, NutritionFacts.org, Full Plate Living, and other Internet sources, as well as purchased videos from Jeff Novick and The Lifestyle Medicine Institute. Each participant receives a notebook of resources and pages to record their progress. The research fellow will collect the data from the clinic participants’ charts, run statistical analysis with Dr. Masato Nakazawa, the co-investigator, do a literature review focused on lifestyle medicine programs, and participate in writing a paper for publication. Research & Scholarly Advancement Fellowship Summer, 2014 Faculty Mentor and Research Project Profile Jody M. Gerome, DO Department of Obstetrics & Gynecology Department of Medical Education OhioHealth O’Bleness Hospital 55 Hospital Dr., Athens (740) 594-9204 Email: [email protected] Project Classification: Clinical Research Techniques and/or skills that the student will learn: 1. Participation in data collection and analysis 2. Participation in the informed consent and randomization process 3. If completed with data collection, participation in the generation of scholarly work for publication 4. Clinical exposure and observation Project Title: Screening and Diagnosis of Gestational Diabetes Project Description: A diagnosis of gestational diabetes mellitus (GDM) is well known to increase the incidence of adverse pregnancy outcomes for both moms and babies. Maternal complications can include hypertensive disorders, increased risk for cesarean section and birth trauma. Infants have an increased likelihood of being large for gestational age, to suffer from jaundice and hypoglycemia and are more prone to operative delivery, shoulder dystocia and birth trauma. At this time, there is not a consensus with regards to the optimal testing used to determine the diagnosis of GDM. While complications are well known, and many feel that diagnosis strategies at this point are inadequate, current opinion suggests that further research should be done before embracing any newly endorsed diagnostic paradigms. Work is ongoing on a prospective, blinded protocol to evaluate two different screening tests for gestational diabetes. Participation in this project will allow for involvement in this innovative trial. Responsibilities would include obtaining informed consent from participants and data extraction from electronic health records. Additionally, a new retrospective protocol which will address outcomes of pregnancies that were diagnosed with GDM by screening in early pregnancy is under development. Participation in this portion would include primarily data collection and synthesis. This project could be accomplished by one or two students, based on availability and interest. Individuals who participate in these projects will have the opportunity to work in a clinical setting, with practicing OB/GYN faculty. This project demonstrates how clinical research can be completed in a community based clinical practice. The chance to shadow in the clinical practice could be available, as well as interacting with patients in the research setting. Research & Scholarly Advancement Fellowship Summer, 2014 Faculty Mentor and Research Project Profile S. Lee Hong, PhD Department of Biomedical Sciences 246 Irvine Hall (740) 593-1041 Email: [email protected] Project Classification: Basic Science, Clinical Research, & Social/Behavioral Research Techniques and/or skills that the student will learn: 1. Psychological/Cognitive Testing 2. EMG 3. EEG 4. Physiological Stress Measurements (Salivary Cortisol) Project Description: The OMNI PIs utilize a team-based model for conducting research. As a result, RSAF students affiliated with Dr. Hong will have to opportunity to work on multiple projects during the summer. Because these studies are fairly large, RSAF students will be able to take the lead on any aspect of any study or project. There are two major efforts that are currently in progress. The first project is a study to measure cognitive task difficulty in young and old. With all standardized tests, two people could receive the same score; one struggled through the test, while the other sailed through. How can the level of difficulty faced by an individual be measured? We plan to examine this problem using measures of motor output, respiration, cardiovascular, and biological measures of stress (salivary cortisol). This project is run in collaboration with the Psychology Department with OMNI Junior Scholar Dr. Peggy Zoccola. The second project seeks to understand the role of the brain in complaints of fatigue in the elderly. We plan to measure EEG activity during physical and mental tasks. Our goal is to test the hypothesis that aberrant patterns of brain activity are the underlying cause of complaints of tiredness in seniors. Research & Scholarly Advancement Fellowship Summer, 2014 Faculty Mentor and Research Project Profile John Kopchick, PhD Department of Biomedical Sciences EBI, Konneker Research Laboratory The Ridges, Athens (740) 593-4534 Email: [email protected] Project Classification: Basic Science Techniques and/or skills that the student will learn: 1. Cloning of Growth Hormone Receptor Genes and mini genes 2. Generation of a targeting vector for disruption of the GHR gene 3. Continuation studies on the heart specific GHR Gene Disrupted mouse 4. Continuation studies on the bone marrow transplantations studies in mice Project Title: The role of the growth hormone receptor (GHR) in heart physiology. Project Description: This project involves generation and subsequent analysis of mice in which the GHR gene is conditionally disrupted, that is, specifically in the heart. Adam Jara, a D.O./Ph.D. student started this project and has generated the mice along with appropriate ‘normal’ controls. Adam will be graduating this coming summer and several experiments will need to be continued after he is gone. In particular, we will continue to monitor the effect of the heart GHR gene disruption of insulin sensitivity and life expectancy. The summer medical student will become intimately involved in the project in that he/she will weigh the mice weekly, determine body composition monthly, perform glucose and insulin tolerance tests bi-weekly, and determine the levels of several hormones and blood constituents monthly (insulin, GH, glucagon, adiponectin, and glucose, IGF-BPs). I anticipate that the student’s name will appear on publications dealing with these mice. Research & Scholarly Advancement Fellowship Summer, 2014 Faculty Mentor and Research Project Profile John Kopchick, PhD Department of Biomedical Sciences EBI, Konneker Research Laboratory The Ridges, Athens (740) 593-4534 Email: [email protected] Project Classification: Basic Science Techniques and/or skills that the student will learn: 1. Cloning of Growth Hormone Receptor Genes and mini genes 2. Generation of a targeting vector for disruption of the GHR gene 3. Continuation studies on the heart specific GHR Gene Disrupted mouse 4. Continuation studies on the bone marrow transplantations studies in mice Project Title: The effect of bone marrow transplant on mouse physiology and aging. Project Description: This project involves the transplant of bone marrow from normal mice to GH transgenic or GHR gene disrupted mice. Dr. Shigeru Okada has already generated the mice and controls for this study. We hypothesize that transfer of ‘normal’ bone marrow to GH transgenic mice (mice with short life spans) will result in mice with normal lifespans. Likewise, we plan to transplant normal bone marrow to GHR gene deleted mice (mice with extended life spans) and expect that this will result in mice with normal life spans. As per the Project #1, the following physiological characterization of the mice will be determined. The summer medical student will become intimately involved in the project in that he/she will perform the bone marrow transfers, weigh the mice weekly, determine body composition monthly, perform glucose tolerance tests weekly, and determine the levels of several hormones and blood constituents monthly (insulin, GH, glucagon, adiponectin, and glucose, IGF-BPs). Also, complete blood counts and differentials will be determined. I anticipate that the student(s) names will appear on subsequent publications dealing with these mice. Research & Scholarly Advancement Fellowship Summer, 2014 Faculty Mentor and Research Project Profile Ramiro Malgor, MD Department of Biomedical Sciences Academic & Research Center 202B (740) 593-2324 Email: [email protected] Project Classification: Basic Science Techniques and/or skills that the student will learn: 1. Cell Culture 2. Immuno Staining 3. Western Blot 4. RT PCR Project Title: Regulation of Wnt5a expression and its role in the pathogenesis of atherosclerosis Project Description: Atherosclerosis (ATH) is a chronic systemic inflammatory disease highly prevalent in the United States which is the major risk factor for cardiovascular disease. Despite concerted efforts in changing lifestyles and the use of new pharmacologic approaches, cardiovascular disease continues to be the principal cause of death in the United States and the rest of the world. The Wnts are a family of secreted glycoproteins that upon binding to their receptors can lead to the activation of various signaling pathways that regulate diverse biological processes including cell proliferation, polarity, differentiation and apoptosis. Wnt5a is a non-canonical non-transforming member of this family that has been implicated in pathogenesis of chronic inflammatory diseases as a macrophage-derived effector molecule, and recently as an inducer of anti-inflammatory (M2) macrophage accumulation and as a blocker of pro-inflammatory (M1) macrophages. We previously reported an association between Wnt5a expression and histopathological severity of human atherosclerotic lesions as well as co-expression of Wnt5a and TLR4 in foam cells/macrophages of murine and human atherosclerotic lesions. Based on these observations, we hypothesize that ox-LDL induces Wnt5a expression through TLR signaling and that this occurs predominantly in M2 macrophages. We also hypothesize that Wnt5a induces smooth muscle cell (SMC) proliferation, migration and production of ECM components. We propose to test our hypotheses through three specific aims: 1: To determine if the transcriptional up-regulation of Wnt5a in macrophages is modulated by TLR signaling. 2: To determine which subset of polarized macrophages are involved in Wnt5a transcription/secretion in atherosclerosis. To approach the problems, a series of in vitro experiments utilizing established cell lines or human monocytes isolated from peripheral blood are outlined. The objectives of this project are to investigate the regulatory pathway and specific type of macrophage involved in Wnt5a expression and secretion as well as its role in the pathogenesis of ATH. The results from this project will provide important information about the cellular and molecular mechanisms involved in the pathogenesis of atherosclerosis, which in turn will help in the development of new therapeutic strategies. Research & Scholarly Advancement Fellowship Summer, 2014 Faculty Mentor and Research Project Profile Ramiro Malgor, MD Department of Biomedical Sciences Academic & Research Center 202B (740) 593-2324 Email: [email protected] Project Classification: Basic Science Techniques and/or skills that the student will learn: 1. Immuno Staining 2. LCM 3. RT PCR Project Title: Wnt5a expression in urothelial carcinoma of the bladder: a novel prognostic marker Project Description: Urinary bladder cancer is the fourth most frequent cancer overall in men in developed countries  and the most common malignancy of the urinary tract. In the United States, it is estimated that there will be 54,610 new cases of bladder cancer and 10,820 deaths in 2013. We recently reported a positive correlation between Wnt5a protein expression by tumor cell and histopathological features of urothelial carcinoma (UC) of the bladder (Malgor et al. Diagnostic Pathology 2013, 8:139). This study suggested a potential application of Wnt5a as a biomarker in the diagnosis and prognosis of UC. Our long term goal is to study the role of the Wnt5a signaling pathway in the pathogenesis of UC. Our working hypothesis is that increased Wnt5a expression is associated with epithelial-mesenchymal transition (EMT) in UC, leading to invasion and metastatic disease. This proposal has the specific objective of evaluating the correlation between Wnt5a expression, histopathological characteristics of aggressiveness and loss of epithelial biomarkers in human UC tissue samples, as well as investigating the Wnt signaling pathways that may be involved. Specific Aim 1: Analyze the correlation between expression of Wnt5a, localization of β-catenin and E-cadherin, and histopathological features in human urothelial carcinoma of the bladder by immunohistochemistry (IHC). Specific Aim 2: Investigate the expression of a panel of Wnt signaling genes in tissue samples of human urothelial carcinoma of the bladder using laser capture microdissection (LCM) followed by RNA extraction and profiler PCR array analysis. This project will provide knowledge regarding the role of Wnt signaling in the pathogenesis of UC. In the first aim we expect to find a positive correlation between increased expression of Wnt5a, loss of expression of E-cadherin and β-catenin from the cell membrane, and histopathological characteristics of aggressiveness, e.g. increase in tumor histological grade or pathological stage. Our second aim will provide information regarding the expression of specific genes related to Wnt mediated signal transduction in UC. Research & Scholarly Advancement Fellowship Summer, 2014 Faculty Mentor and Research Project Profile Felicia V. Nowak, MD/PhD Department of Biomedical Sciences 228 Irvine Hall (740) 593-2223 Email: [email protected] Project Classification: Basic Science Techniques and/or skills that the student will learn: 1. Cell Culture 2. Transfection with siRNA, selection and development of stable knock-down cell lines 3. Processing cells for protein extraction and RNA isolation 4. Western Blots 5. PCR Project Title: Role of Insulin and IGF-1 Receptors in Regulation of the Pro-apoptotic Factor, Porf-2 Project Description: Preoptic regulatory factor-2 (Porf-2) is a RhoGAP domain-containing protein that has been shown to inhibit proliferation and enhance apoptosis in neural stem cells. It is expressed in renal cortex and medulla, and expression is up-regulated in the diabetic kidney, but the role of Porf-2 in diabetic nephropathy (DN) has not been established. In vitro, we have demonstrated that both insulin and insulin like growth factor-1 (IGF-1) suppress expression of PORF-2. We have also shown that specific inhibitors of IGF-1 and insulin intracellular signaling pathways reverse the suppression of Porf-2. However, studies on the receptors for insulin (IR) and insulin growth factor-1(IGF-1R) have not been conducted. The purpose of this study is to knock down the insulin and IGF-1 receptor mRNAs to confirm their role in modulation of Porf-2 expression. Identification of these mechanisms will open new avenues for development of novel diagnostic, therapeutic and preventative strategies for regulation of apoptotic factors in diabetic kidney. The significance of the proposed work is that we have identified a pro-apoptotic factor with a potential role in DN. The specific aim of this project is to investigate the role of the insulin and IGF-1 receptors on expression of the Porf-2 gene. In a normal kidney, Porf-2 expression is suppressed by insulin. Currently, the role of pro-apoptotic Porf-2 expression in diabetic nephropathy is not clear. In a diabetic kidney, Porf2 expression may increase because insulin signaling is impaired. This increase in Porf-2 may promote the worsening of DN. The overall hypothesis is that a change in Porf-2 expression contributes to the pathogenesis of diabetic nephropathy. Our previous work has shown that Porf-2 expression in diabetic kidney is decreased in animals with better preservation of renal function due to ingestion of an antioxidant fortified diet. During initial studies of Porf-2 expression in FRTL-5 cells, we also observed that in media containing physiological levels of insulin or IGF-1, the expression of Porf-2 was decreased. Insulin, as does IGF-1, binds to both IR and IGF-1R to exert its biological effects on metabolism and growth via two major pathways- PI3K/AKT and MAPKK pathways. We have shown that inhibition of specific intracellular mediators in these pathways blocks the down-regulation of Porf-2 by IGF-1. We will test the specific hypothesis that insulin/IGF-1 effects on Porf-2 are mediated through IR and IGF-1R receptors and knock down of these receptors will abrogate the effect of insulin and IGF-1 on proapoptotic Porf-2. Cell lines in which IGF-1R has been knocked down have already been analyzed for levels of IGF-1R by polymerase chain reaction (PCR) and the effects on Porf-2 expression. Knockdown of IGF-1R resulted in an increase in Porf-2 expression. Initially we will generate at least one and preferably two stable cell lines in which IR is knocked down to 60% of wild type. Western blots will be performed to quantify the level of IR being expressed. We will also complete the studies on IGF-1R depleted cells by Western blot analysis of IGF-1R. PCR will be conducted to quantify the levels of IR mRNA. We will then determine the effects of depletion of IRs on the expression of the Porf-2 gene, by PCR. Samples with intact IR will be compared to samples from cells where IR expression has been decreased by at least 60%. Research & Scholarly Advancement Fellowship Summer, 2014 Faculty Mentor and Research Project Profile Jay Shubrook, DO Department of Family Medicine/Diabetes Institute 320 Grosvenor Hall (740) 593-2137 Email: [email protected] Project Classification: Clinical Research Techniques and/or skills that the student will learn: 1. Provision of diabetes education 2. Clinical management of diabetes 3. Clinical research design, data collection, data analysis and dissemination Project Title: Advancing Diabetes Care through Awareness, Compliance and Education (ADVANCE) Project Description: The worldwide burden of diabetes mellitus is increasing at an alarming rate. Even with numerous public awareness campaigns directed at patients and health care providers, the major targets of diabetes management, namely hemoglobin A1c, blood pressure, and cholesterol, are inadequately controlled. There are many factors that contribute to the complexity of diabetes management, such as communication between health care providers and patients, patient knowledge and awareness of diabetes and the potential long-term complications, health literacy, and non-adherence with diabetes interventions. Interventions to address these barriers have had limited success, particularly when it comes to successful and practical utilization outside of the study setting. Diabetes is largely self-managed. However, very few people have the knowledge and skill set to properly self-manage diabetes. This requires intensive initial education and ongoing refresher courses to maximize self-care. Physicians typically have little time for discussions of risk reduction and diabetic complications due to many issues, such as competing illnesses, medication management, test orders, required documentation, and health maintenance. In addition, physicians do not feel that they have the time or expertise to provide proper lifestyle counseling. Even though many patients are referred for diabetes education, most do not go. There is a myriad of reasons for this. Cost of the program is typically not covered in Ohio, time needed for classes may be too long, the person may not fell that they need education. All in all about 25% of people diagnosed with diabetes ever receive diabetes education. Currently, diabetes education is most often offered by diabetes educators in a set class of 8-12 hours. As a result the volume of info for most diabetes education sessions is more than a person can absorb. We propose a diabetes education intervention in a convenient, patient-friendly and readily available manner. We plan to provide patients with focused diabetes education, i.e. education on one aspect of management or one complication of diabetes per office visit, allowing time for review of the materials provided and review of any questions at the next office visit. We also plan to incorporate a cell phonebased system for patients to deliver information on their blood sugars and body weights to their providers on a weekly basis. This system will deliver weekly reminder messages to those patients who fail to respond. Also, a weekly statement or “bullet point” from the educational material covered will be delivered. Finally, we will encourage the participation of family members in these interventions, not only to improve the patient’s self-management, but also as a means to deliver the same educational message to other people who are likely at risk for or have diabetes. The student involved in this project will be involved in the implementation of the programs at the diabetes center and local primary care offices, the collection and analysis of the data. They will be involved in diabetes clinical care and diabetes education-through classes and the proposed intervention. They will gain valuable insight into optimal ways to share information with patients and improve self-care and adherence. Research & Scholarly Advancement Fellowship Summer, 2014 Faculty Mentor and Research Project Profile Jay Shubrook, DO Department of Family Medicine/Diabetes Institute 320 Grosvenor Hall (740) 593-2137 Email: [email protected] Project Classification: Clinical Research Techniques and/or skills that the student will learn: 1. Clinical diabetes management 2. Clinical research design, data collection, data analysis and dissemination 3. Harvesting of existing data Project Title: The Effectiveness of the CHIP program in those with type 2 Diabetes Project Description: Therapeutic lifestyle changes focusing on diet, exercise and tobacco could prevent about 40% of all cancer deaths and 82% of cardiac deaths in the US. It is estimated that 71% of colon cancers, 70% of strokes, and 91% of diabetic cases could be avoided by living a healthy lifestyle. Chronic diseases that affect Western populations add a tremendous burden to our healthcare budget, and to the loss of productivity of our society. In 2007, an estimated $2.3 trillion was spent on healthcare in the US, or approximately $7,600 for each individual. Projections are that without dramatic change, this cost will continue to increase to unsustainable levels. The Complete Health Improvement Program (CHIP) is a lifestyle medicine program with proven effectiveness in addressing the problem of chronic disease experienced in those who live the Western lifestyle. Poverty complicates this further. Athens County is struggling with the highest poverty rate in Ohio at 32.8% with nearly 18% of the population uninsured. Many people in poverty, have significant health issues, and struggle with other disadvantages and insufficiencies, which may include lack of transportation, lack of sufficient housing, limited education, mental illness and limited access to health care. These socioeconomic factors also increase their risk for diabetes. Type 2 diabetes is an American epidemic that currently affects 1 in 8 adults. It is projected that this will increase to 1 in 3 adults by 2030. Type 2 diabetes is a chronic disease that is largely preventable and wholly treatable. Most effective early interventions have been lifestyle based. In the proposed study we will evaluate both the Athens area CHIP program data as well as the national CHIP data for the effect of this therapeutic lifestyle program on people with type 2 diabetes. The student researcher will be trained on the CHIP program, will learn to explore existing data sets, and do a subanalysis for those participants who have diabetes. They will gain valuable information about chronic disease management and will be able to apply clinical research to the community setting-bedside to community and ultimately population health.